Vanadate oxide and silanol catalyst system

ABSTRACT

Process for converting secondary and tertiary acetylenic carbinols to the corresponding alpha,beta-unsaturated carbonyl compounds by rearranging the carbinol with (trilower alkyl-, tricycloalkyl-, triaryl- or triarylalkyl-siloxy) vanadium oxide catalyst in the presence of a silanol.

United States Patent Andrews et al.

[ 1 Oct. 14, 1975 VANADATE OXIDE AND SILANOL CATALYST SYSTEM Inventors:David Arthur Andrews, Upper Montclair, N.J.; Nathan Chadwick Hindley,Welwyn Garden City,

England Assignee: Hoffmann-La Roche Inc., Nutley,

Filed: Oct. 29, 1973 Appl. No.: 410,930

Foreign Application Priority Data Nov. 2, 1972 United Kingdom 50558/72US. Cl 252/431 R; 260/3409; 260/397.47;

260/476; 260/488; 260/593 R; 260/601 R Int. Cl. B01J 31/12 Field ofSearch. 252/431 R; 260/60] R, 593 R [5 6] References Cited UNITED STATESPATENTS 3,046,269 7/1962 Cohen et a1 252/431 R X 3,324,195 6/1967 Hwa etal 252/431 R X 3,468,865 9/1969 Santiago 252/431 R X 3,642,748 2/ 1972lwasaki et al. 252/431 R X Primary ExaminerPatrick P. Garvin Attorney,Agent, or FirmSamuel L. Welt; Jon S. Saxe; William H. Epstein 4 Claims,No Drawings VANADATE OXIDE AND SILANOL CATALYST SYSTEM CROSS REFERENCETO RELATED APPLICATIONS Related to this application is US. patentapplication Ser. No. 248,046, filed Apr. 27, I972. Pauling.

BACKGROUND OF THE INVENTION Certain alpha,beta-mono-unsaturatedaldehydes have heretofore been obtained by the catalytic rearrangementof corresponding tertiary acetylenic carbinols or derivatives thereof.For example, acetylenic carbinols have been converted to unsaturatedaldehydes by a process involving initially esterifying the carbinols andthen rearranging the ester derivative with the aid of a silver or coppercatalyst. Typically, such rearrangement reactions have required severalprocess steps, including the formation of an allene ester intermediate.

In an effort to reduce the number of process steps required for suchcatalytic rearrangement processes, catalysts derived from a metal of theVth or VIIth subgroup of the periodic chart, particularly vanadium,niobium, molybdenum, tungsten and rhenium, have been utilized instead ofcopper or silver catalysts. See British Pat. No. 1,204,754. Suchcatalysts have permitted acetylenic carbinols to be expeditiouslyrearranged to unsaturated aldehydes in a single operation. However, theuse of such catalysts of the Vth to VIIth sub-group has not been foundto be completely satisfactory. Considerable loss of catalyst activityhas been found to inevitably occur during the course of therearrangement reaction. In addition, it has been discovered thatdecomposition products are formed during the rearrangement reaction asthe catalyst loses activity and that these decomposition products causethe aldehyde product to be destroyed as it is formed, thereby reducingproduct yields.

SUMMARY OF THE INVENTION In accordance with this invention, a process isprovided for obtaining alpha,beta-unsaturated carbonyl compounds of theformula:

c c--R, H

wherein R,. R and R are as above; in the presence of a catalyst of theformula:

wherein R, is lower alkyl, higher alkyl, cycloalkyl. aryl or aryl loweralkyl, said cycloalkyl or aryl being unsubstituted or substituted withlower alkyl; R is R, or (R,);,Si'; m is an integer of from I to 3; and nis an integer of from 0 to 2, with the proviso that the sum of m and nis 3; and a silanol of the formula:

wherein R is lower alkyl, higher alkyl, cycloalkyl aryl or aryl loweralkyl, with said cycloalkyl or aryl being unsubstituted or substitutedwith loweralkyl.

It has been found that the use of the silanol of formula IV in theconversion of a compound of formula II to a compound of formula I suchas disclosed in US. patent application Ser. No. 298,046, filed Apr. 27.I972, Pauling, reduces any loss of the activity of the catalyst offormula III. Therefore, this catalyst can be reused for many subsequentreaction batches without any loss of yield of the compound of formula Iproduced by this process. Furthermore, the use of the silanol of formulaIV in the reaction medium minimizes the production of decompositionproducts which would reduce the yields of the compound of formula I.Therefore, the use of the compound of formula IV in the reaction mediumpermits the catalyst to be reused over and over again without anydeactivation or loss of yield of the compound of formula I.

Furthermore, a catalyst system is provided in accordance with thisinvention containing the catalyst of formula III and the silanol offormula IV. This system, which is utilized for the rearrangement of thecompound of formula II can be reused, after removal of the rearrangementproduct, the compound of formula II, by simply adding another batch ofthe compound of 'formula II to this system.

DETAILED DESCRIPTION OF THE INVENTION As used throughout thisapplication, the term hydrocarbyl denotes a monovalent, straight chainor branched chain aliphatic substituent consisting solely of carbon andhydrogen. The hydrocarbyl group can be saturated or unsaturated in oneor more positions. Among the hydrocarbyl groups are included alkylgroups containing from 1 to 30 carbon atoms and alkenyl and alkynylgroups containing from 2 to 30 carbon atoms. The alkyl groups can beunsubstituted or substituted in one or more positions with lower alkyl,lower alkoxy, hydroxy, oxo, ketalized oxo, lower alkanoyl, aroyl, loweralkanoyloxy, or aroyloxy groups. Among the preferred hydrocarbyl groupsare included lower alkyls and groups having an isoprene or isoprenelikestructure. Among the preferred substituted or unsubstituted hydrocarbylgroups denoted by R and R are included:

methyl;

4-methyl-pent-3-enyl;

3.4-dimethyl-pent-3-enyl;

l-ethyl-4-methyl-pent-3-enyl;

4-hydroxy-4-methyl-pentyl; 4-methoxy-4-methyl-pentyl;4,8-dimethyl-nona-3,7-dienyl; 4,8.1Z-trimethyl-tridecyl; and

4,8, l 2-trimethyl-trideca-3,7,l l-trienyl.

As also used throughout this application, the term cyclohydrocarbyldenotes a monovalent, mono-or poly-cycloaliphatic or aryl substituentconsisting solely of carbon and hydrogen. The cycloaliphatic group canbe saturated or unsaturated in one or more positions. Thecyclohydrocarbyl substituent defined by R R and R can be unsubstitutedor substituted in one or more positions with lower alkyl, lower alkoxy,hydroxy, oxo, ketalized x0, lower alkanoyl, aroyl, lower alkanoyloxy oraroyloxy groups. The substituted and unsubstituted cyclohydrocarbyl caninclude from 3 to 30 carbon atoms. Among the preferredmonocycloaliphatic substituents which are defined by R R and R areincluded the cycloalkyl or cycloalkenyl groups containing from 3 tocarbon atoms, i.e., cyclohexyl, cyclopropyl, .cycloheptyl,3-methyl-cyclohex-3-en-l-yl; and 4-methyl-cyclohex-3-en-l-yl andcyclohexenyl. Among the preferred aryl substituents which are defined byR,, R and R being cyclohydrocarbyl is phenyl and naphthyl. In thecompounds of formula ll where R, and R are joined together to form anunsubstituted or substituted monocycloaliphatic substituent, thepreferred compounds are:

1 -ethynyl-cyclopentanol;

l-ethynyl-cyclohexanol;

l-ethynyl-2,6,6-trimethyl-cyclohexanol;

4-ethynyl-4-hydroxy-1-oxo-3 ,5 ,5-trimethylcyclohex-2-ene; and4-ethynyl-4-hydroxy-l l -ethylenedioxy-3,5,5-

trimethyl-cyclohex-2-ene.

The term cyclohydrocarbyl also includes polycycloaliphatic substituents,i.e., a cycloalkyl group condensed with one or more saturated orunsaturated cycloalkyl groups. Where R, and R taken together with theirattached carbon atom form a cyclohydrocarbyl substituent, thesubstituent can be a monocycloaliphatic group or a monocycloaliphaticgroup condensed with one or more cyclohydrocarbyl groups. These groupsinclude:

l 7alpha-ethynyl-3 beta,l 7beta-dihydroxy-androst- S-ene;l7alpha-ethynyl-l 7beta-hydroxy-l 3beta-methylgon-5( l0)-en-3-one; andnorgestrel. As further used throughout this application, the termcyclohydrocarbyl substituted hydrocarbyl denotes cyclohydrocarbylsubstituted hydrocarbyl groups wherein cyclohydrocarbyl and hydrocarbylare defined asabove. Both the cyclohydrocarbyl and hydrocarbyl groupscan be unsubstituted or either one or both of the hydrocarbyl andcyclohydrocarbly groups can be substituted in one or more positions withlower alkyl, lower alkoxy, hydroxy, oxo, ketalized oxo, lower alkanoyl,aroyl. lower alkanoyloxy or aroyloxy.

Among the preferred cyclohydrocarbyl substituted hydrocarbylsubstituents defined by R and R are the groups wherein the hydrocarbylmoiety has an isoprene or isoprene-like structure. such as:

2-(2,6.o-trimethyl-cyclohcx-l-en-l-yl)-vinyl;2(4-oxo-2,6.6-trimethyl-cyclohex-l-en-l-yl )-vinyl; 2-(4 4ethylenedioxy2,6,6-trimcthyl-cyclohex-l -enl-yl)-vinyl; 6-(2.6,6-trimethyl-cyclohex- 1 -en- 1 -yl )-4-methylhexan-l .3,5-trienyl;6-(4-oxo-2,6.6-trimethyl-cyclohex-l-en-l-yl)4- methyl-hex-l,3.5-trienyl;and

6-( 4.4-ethylenedioxy-2.6,6-trimethyl-cyclohex- 1-enl-yl)-4-methyl-hexa-l .3,5-trienyl groups.

Among the substituted and unsubstituted hydrocarbyl groups defined by Rare:

p py

2-hydroxy-prop-2-yl; and

2,6-dimethyl-hepta-l ,3,5-trienyl.

As further used throughout this application, the term lower alkylcomprehends branched chain and straight chain, saturated aliphatichydrocarbyl groups containing 1 to 7 carbon atoms, such as methyl,ethyl, propyl and isopropyl. As also used herein, the term lower alkoxy"comprehends lower alkyloxy groups containing 1 to 7 carbon atoms such asmethoxy and isopropoxy. As further used herein; the term lower alkanoyl"comprehends lower alkyl acyl groupscontaining 1 to 7 carbon atoms suchas formyl, acetyl, propionyl, and butyryl. As still further used herein,the term aroyl comprehends monocyclic, aromatic hydrocarbon acyl groupswhich may be unsubstituted or substituted in one or more positions withlower alkyl.

The preferred aroyl is benzoyl. Also herein, the term lower alkanoyloxycomprehends lower alkyl acyloxy groups containing 2 to 7 carbon atomssuch as acetoxy and propionyloxy. Further herein, the aroyloxycomprehends groups such as benzoyloxy. Still further herein, the term.cycloalkyl" comprehends cycloaliphatic groups of 3 to 7 carbon atoms,such as cyclohexyl. Also herein, the term aryl signifies mono nucleararomatic hydrocarbon groups such as phenyl, tolyl, etc., which can beunsubstituted or substituted in one or more positions with lower alkyl,or polynuclear aryl groups such as naphthyl, anthryl, phenanthryl,azulyl, etc., which can be unsubstituted or substituted with one or moreof the aforementioned groups. The preferred aryl substituents are phenylor naphthyl which can be unsubstituted or substituted in one or morepositions with lower alkyl.

In the compound of formula ill,

II! I wherein R R and R have the same meaning as R and in the compoundof formula W wherein R R and R have the same meaning as 6 As stillfurther used throughout this application, the wherein R, and R are takentogether with their atterm aliphatic, with reference to a hydrocarbyl orcytached carbon atom to form an unsubstituted cycloaliclohydrocarbylgroup, denotes substituents containing phatic substituent or substitutedwith lower alkyl, lower no aromatic unsaturation but which can beotherwise alkoxy, hydroxy, oxo or ketalized oxo; compounds of saturatedor unsaturated, ie, an alkyl or a group con- 5 the formula: tainingolefinic and/or acetylenic unsaturation. Also herein, the term ketalizedoxo" comprehends deriva- O tives of an oxo group formed by reactionthereof with t R-," H

a lower alkanediol, preferably ethylene glycol, or a [3 lower alkanol,preferably methanol, to yield a lower alkylenedioxy group. The preferredlower alkylenewherein R is unsubstituted cyclohydrocarbyl or cydioxygroups are the groups having 1 to 4 carbonclohydrocarbyl substitutedwith lower alkyl, lower alkatoms, particularly methylenedioxy andethylenedioxy. oXy, hydroxy, oxo or ketalized oxo; unsubstituted and Thegroup designated by R in the compound of forhydroxyand alkoxysubstituted compounds of the formulae Ill and IV is preferably a loweralkyl group con- 1 mula:

taining from l to 7 carbon atoms, i.e., methyl, ethyl, wherein R ishydrogen or lower alkyl; a= l, h= l and isopropyl or n-butyl; a phenylor naphthyl group which c l or u 0, I2 l and c l or u 0, b 0 and can beunsubstituted or substituted in one or more posil or u 0, I2 0 and r- 0;and the dotted bonds can tions with lower alkyl (tolyl or xylyl).Furthermore, R, be optionally hydrogenated and wherein hydroxy and canbe a phenyl lower alkyl group such as benzyl or 1 lower alkoxysubstituents may be present in the group phenethyl or a higher alkylgroup containing from 8 to ings u, I; and c; compounds of the formula:

20 carbon atoms such as decyl, dodecyl, octyl, pentawherein d is aninteger ofO to l; X is hydroxy or hydrodecyl, octadecyl, etc. gen; and Yis oxo or hydrogen; and compounds of the Among the importantalpha,beta-unsaturated carformula:

H Y IE bonyl compounds of formula I are included compounds wherein X islower alkyl; Y is hydrogen or lower alkyl; of the formula: Z is hydroxy,oxo, ethoxy or acyloxy, and wherein the A-ring can be saturated orwholly or partially unsaturated and the B-ring can be saturated orpartially unsat- O A urated. I -bk/J The acetylenic carbinols of formulall utlllzed as starting materials in the process of this invention forconversion to the preferred carbonyl compounds of formulae lA, lB, IC,[D and 1E hereinbefore, are compounds of the formula llA wherein R, andR are as above;

llB

wherein R is as above;

wherein R;,', a, b, c and the dotted bonds are as above; and whereinhydroxy and lower alkoxy substituents may be present in the groupings u,I; and c;

IID

wherein Y, X and d are as above; and

IIE

wherein X, Y and Z are as above; and the A-ring can be saturated orwholly or partially unsaturated and the B-ring can be saturated orpartially unsaturated.

The process of the present invention has proved to be particularlyfavorable and advantageous for the manufacture of the following x0compounds:

Senecioaldehyde (prenal);

3-methyl-pent-2-en- 1 -al;

3 ,7-dimethyl-4-ethyl-octa-2,6-dien- 1 -al;

3,7-dimethyl-7-methoxy-oct-2-en-l-al;

non-2-enl-al;

citral;

7-hydroxy l-al);

alpha-citral(3,7-dimethyl-oct-7-en-l-al);

farnesal;

phytal;

cyclohexylidene-acetaldehyde;

2,6,6-trimethyl-cyclohexylidene-acetaldehyde;

cinnamaldehyde;

beta-C -aldehyde;

vitamin A aldehyde;

2-methyl-hept-2-en-4-one;

2,5-dimethyl-hex-2-en-5-ol-4-one;

l7-formylmethylene-3betahydroxy-androst-5-ene;

l7-formylmethylenel 3beta-methyl-gon-5( 10 )-en- 3-one: and

citral( 7-hydroxy-3 ,7-dimethyl-oct-6-enl3beta-ethyl-l7-formylmethylene-gen-4-en-3-one.

Of the catalysts of formula Ill employed in accordance with the presentinvention, those of the general formula:

wherein R is as above; occupy a preferred position. In an especiallypreferred aspect, R is an alkyl or phenyl group. Particular examples ofcatalysts of formula lllA are:

tris-(trimethyl-siloxy)-vanadium oxide; and

tris-(triphenyl-siloxy)-vanadium oxide.

tris-(tricyclohexyl-siloxy)-vanadium oxide.

The catalysts of formulae lll and "IA are known compounds. They can beprepared according to methods known per se; for example. by

i. the reaction of, for example, vanadium pentoixde with, for example, atrialkyl silanol of the formula (alkyl) SiOH or a triaryl silanol of theformula (aryl)- SiOH or a tricycloalkyl silanol with azeotropic removalof the water formed in the reaction with the aid of an extraining agentsuch as, for example, benzene.

ii. the reaction of, for example, vanadium oxytrichloride with, forexample, a trialkyl silanol or triaryl silanol or tricycloalkyl silanolin the presence of a base such as pyridine or ammonia;

iii. the reaction of, for example, vanadium oxytrichloridewith, forexample, a trialkyl alkali silanolate of the formula (alkyl) SiOME(l) ora triaryl alkali silanolate an alkali metal.

iv. The reaction of, for example, a vanadium acid ester of the formula(alkoxy) ,-V=O with, for example, a trialkyl silanol or triaryl silanolor tri(cycloalkyl silanol in the presence of catalytic amounts of analkyl-, arylor cycloalkyl alkali silanolate (e.g.. a trialkyl alkalisilanolate).

v. the reaction of, for example, silver orthovanadate of the formula AgVO with, for example, a trialkyl silyl halide of the formula (alkyl)SiCl or a triaryl silyl halide of the formula (aryl) SiCl in a solventsuch as, for example, benzene or methylene chloride;

vi. the reaction of, for example, vanadium pentoxide with, for example,a hexaalkyl disiloxane of the formula (alkyl) SiOSi(a1kyl) at anelevated temperature, for example at about 100C or vii. the doublereaction of a vanadium acid ester of the formula (alkoxy)3V=O with atrialkyl silyl ester or triaryl silyl ester, for example, of tripropylorthovanadate with trimethyl silyl acetate with the expulsion of propylacetate.

The catalyst system used in the isomerization reaction can be preparedby mixing the silanol of formula IV and the vanadate catalyst of formulaIII. This mixture which is utilized to isomerize the compound of formula11 contains at least 0.05 mole percent of the silanol of formula IVbased upon the moles of the vanadate catalyst of formula III in themixture. The mixture utilized to isomerize the compound of formula IIcan contain a large excess of silanol, i.e., 85,000 mole percent orgreater of the silanol of formula IV, based upon the mole percent of thevanadate catalyst of formula III. Generally, it is preferred that themixture contain from about 5 mole percent to 65,000 mole percent of thesilanol of formula IV, based upon the moles of the vanadate catalystcontained in the mixture. Mixtures containing from 25 mole percent to8,500 mole percent of the silanol of formula IV based on the moles ofthe vanadate of formula III are especially preferred. The compound offormula II can be added to the mixture or the mixture can be added tothe compound of formula II in order to carry out the isomerizationreaction.

The catalytic isomerization of acetylenic carbinols of formula II toalpha,beta-unsaturated oxo compounds of formula I in accordance with thepresent invention is expediently carried out by reacting thecorresponding carbinol together with the catalyst system containing thevanadate catalyst and slanol of formula IV. The catalytic isomerizationis expediently carried out using about 0.1 to about mole percent,preferably about 1.5 to about 2 mole percent of catalyst of formula 111based on the moles of the compound of formula II.

The silanol of formula IV is present in the reaction mixture in anamount of about 0.01 mole percent based upon the moles of the compoundof formula 11 up to an amount in which it takes on the function of asolvent. An addition of 1-85 mole percent, especially 5-65 mole percentof silanol is preferred. The mole percent of silanol is based on themoles of the compound of formula II.

The siloxy moiety of the silanol of formula IV need not be identicalwith the siloxy moiety of the catalyst of formula 111. When a silanoland catalyst having different siloxy moieties are used there isgenerally formed the most stable compound from the thermodynamic pointof view. Thus, for example, tris-[tri(npropyl)-siloxy]-vanadium oxide isconverted into tris- (triphenyl-siloxy)-vanadium oxide by the additionof triphenyl silanol.

The present catalytic isomerization can be carried out in an inertsolvent and in the presence of, or with the exclusion of air. As thesolvent, any conventional inert organic solvent can be utilized.Suitable solvents are, for example, aliphatic hydrocarbons such as, forexample, heptane, cyclohexane, cyclododecane, decalin, paraffin andparaffin oil, aromatic hydrocarbons such as, for example, benzene,nitrobenzene, toluene and xylene, halogenated hydrocarbons such as, forexample, chlorobenzene, ethers such as, for example, anisole or dioxaneor amines. Polymeric siliconcontaining solvents such as silicon oilscontaining aliphatic or aromatic groups (e.g., methyl phenylpolysiloxane) can also be used. As mentioned earlier, a silanol offormula IV can be added to the mixture in an excess amount and can thusalso serve as a solvent. Therefore, any excess of the silanol of formulaIV can be utilized in carrying out this reaction.

In carrying out this rearrangement reaction, temperature and pressureare not critical, and this reaction can be suitably'carried out at atemperature of between about room temperature (22C.) and the boilingpoint of the reaction mixture and at atmospheric pressure. Preferably,the reaction is carried out at a temperature between 50C. and 200C.,with a temperature of about C. to 160C. being particularly preferred. Ifdesired, the isomerization can also be carried out under pressure, inwhich case pressures of from 1 atmosphere to about 50 atmospheres can beused. Also, the isomerization time can vary within wide ranges. Ingeneral, it amounts to about 2-20 hours. If desired, reaction times ofhours or longer can be utilized without deleteriously affecting thisreaction. However, since there is no additional beneficial results fromprolonged heating, the use of long reaction times only adds additionalexpense to carrying out the reaction. The catalyst system containingsiloxy vanadium oxide catalyst and silanol employed in the presentisomerization retains practically its complete activity during theisomerization. It can therefore be used again for carrying out many (ca100-200) isomerization batches.

The isomerization product is separated from the unreacted portions ofthe carbinol starting material in the usual manner; for example, byrectification. The unreacted carbinol portions can again be employed inthe next batch. With this procedure there are obtained, in general,conversions of 70 to 99.9%, and, depending on the carbinol startingmaterial employed, yields of more than 90%.

The following examples are illustrative but not limitative of theinvention. All temperatures are in degrees centrigrade. The namedehydrolinalool designates the compound 3,7-dimethyl-oct-6-en-1-yn3-ol.

EXAMPLE 1 15.2 g of dehydrolinalool, 1.3 g oftris-[triphenylsiloxyl]-vanadium oxide, 5.5 g of triphenyl silanol and100.0 ml of high-boiling paraffin oil [D 0.885] are heated to C. in anitrogen atmosphere for about 4 hours. The mixture is subsequentlycooled to 70C. and, at this temperature, subjected firstly to a simpledistillation and thereafter to a vacuum distillation [0.1 mmHg]. In thelast 30 minutes of the distillation the temperature is increased to140C. so that all liquid components distill over. The residualcatalyst/paraffin oil mixture can again be employed, asmcntionedearlier, for the isomerization of further 15.2 g batches ofdehydrolinalool. The results of isomerizations carried out with the samecatalyst are given in the following Table:

Table lsomerization of dehydrolinalool lDLL-OH] to citral with the aidof tris-[triphenyl-siloxyl vanadium oxide 124.5 g of pyridine aredissolved in 1350 ml of benzene. A solution of 82.5 g of vanadiumoxychloride in 1350 ml of benzene and a solution of 414.6 g of triphenylsilanol in 4500 ml of benzene are simultaneously introduced withstirring into the resulting solution in the course of 2.5 hours. In sodoing, the temperature rises from 21C. to about 31C. The mixture isstirred for a further 3 hours without cooling. The precipitated pyridinehydrochloride is filtered off. The filtrate is concentrated. Thecrystal-mass obtained is taken up in 3000 ml of diethyl ether. The tris-[triphenyl-siloxy]-vanadium oxide which separates out in crystallineform is filtered off, washed with diethyl ether and dried in a vacuum at40C.50C. Melting point 224226C.

EXAMPLE 3 By the procedure of Example 2 there can be prepared, interaliaz from vanadium oxychloride and trimethyl silanol thetris-[trimethyl-siloxy]-vanadium oxide b.p.: 103105C/1O mmHg. fromvanadium oxychloride and ethyl dimethyl silanol thetris-[ethyl-dimethyl-siloxy]-vanadium oxide from vanadium oxychlorideand diethyl methyl silanol 12 b.p.: 73-74C/3 mmHg.

1 EXAMPLE 4 V 462 ml of paraffin oil [D 0.855], 15.2 g of tri- 5 phenylsilanol and 31.3 g of dehydrolinalool are mixed from vanadiumoxychloride and a mixture offl part of I trimethyl silanol and 2 partsof isop ro p a nolithe trimethyl-siloxy]-bis-(isopropoxy)-vanadium oxidetogether with stirring and heated to 140C. in an atmosphere of air or inan inert gas atmosphere. The clear, light-yellow colored solution whichresults after the addition of 4.3 g of tristriphenyl-siloxy-vanadiumoxide is stirred at 140-142C. for 4 hours. The mixture is thereaftercooled to about C. and distilled under reduced pressure [0.1-0.5 mmHg].The citral which passes over at 5060C., l mmHg, is distilled offcompletely. The temperature is thereby raised to about 140C. for about15 minutes towards the end of-the distillation.

After the removal of the citral, a new isomerization batch can beproceessed immediately by treating the residual paraffin oil/catalystmixture at 140C. with 31.3 g of dehydrolinalool as previously described.The results thereby obtained are given in the following Table:

g of 3-methyl-but-l-yn-3-ol and 80 g of triphenyl silanol are heated toC. for 7 hours in 2800 ml of paraffin oil [D 0.885] and the mixture istreated at this temperature with 40 g of tris-[triphenyl-siloxy1-vanadium oxide. The mixture iscooled to about 78C. and distilled underreduced pressure, the pressure being lowered to 5 mmHg towards the endof the distillation. The prenal [3-methyl-but-2-en-l-al]' which isformed boils at l32-133C/730 mmHg.

The residual mixture. consisting of the paraffin oil employed and thetris-[triphenyl-siloxyl-vanadium oxide and triphenyl silanol can againbe employed for the isomerization of further 120 g batches of3-methyl-but-l-yn-3-ol. The results obtained in this series ofexperiments are given in the following Table:

13 EXAMPLE 6 The following isomerizations can be carried out by theprocedure described in Example 4.

3-methyl-pent-l-yn-3-o1 Yield 3-methy1-pent-2-en-l-al b.p.: 60C./35mmHg. 3,6.7trimelhy1-oct-6-en-1-yn-3-ol3.6,7-trimethyl-oct-2.6-dien-1-a| b.p.: 60"c./0.3 mmHg.3.7-dimethyl-7-methoxy-oct-1-yn-3-o1 3.7-dimethyl-7-methoxy oct-2-en- 1-al b.p.: 66C./0.1 mmHg. 2,6-dimethyl-oct-7-yn-2.6-dio1l7-hydroxydehydrolinaloo1] 3.7dimethyl-oct-2-en-7-ol-1-a1[7-hydroxycitral] b.p.: 98C./0.3 mmHg. l-ethynyl-cyclohexanol a)cyclohexylidene-acetaldehyde b.p.: 48C./1.3 mmHg.

b.p.: 48C./1.3;mmHg. l-ethynyl-2.6,6-trimethyl-cyclohexanol a)2.2.6-trimethy1-cyclohexylidineacetaldehyde b) 2.2,6-trimethy1cyc1ohex-l-en-lyl-acetaldehyde b.p.: 50c./0.1 mmhg.

1 -ethynyl-cyclopentano1 cyclopentylidene-acetaldehyde b.p.: 30C./0.1mmHg.

b.p.: 34C./0.25 mmHg. 2,5-dimethy1-hex-3-yn-2.S-diol2.5-dimethyl-hex-2-en-5-ol-4-one b.p.: 35C./0.2 mmHg.

3.7.1 1-trimethyl-d0deca-6,10-dien-1-yn-3-ol ldehydronerolidol] 3.7.11-lrimelhy1-dodeca-2.6,lO-trien-l-al lfarnesal] b.p.: 86C./0.2 mmHg.

3,7,1 1.15-tetramethyl-hexadeca-6,l0,l4-trien-1- yn-3-olldehydrogeranyllinalool] 3,7,1l.15-tetramethyl-hexadeca-2.6,10,14-tetraen- 1-al [geranylcitral] 3,7,11, 1 5-tetramethy1-hexadec- 1 -yn-3-o1 [dehydroisophytol] 3 ,7.11.1S-tetramethyl-hexadec-2-en- 1 -al lP Y l b.p.: 150C./0.3 mmHg.

EXAMPLE 7 A mixture of 15.2 g of 3-hydroxy-3,7-dimethyl-octa- 6-en-l-yne[dehydrolinalool], 0.52 g of tris-[trimethylsiloxy]-vanadium oxide, 5.5g of triphenyl silanol and 200 g of liquid paraffin (b.p. 170C/0.1 mmHg)are heated to 140C. under an inert gas atmosphere for 4 hours. Thecitral formed is separated from the unreacted dehydrolinalool byrectification. The conversion of dehydrolinalool amounts to 92%. Theyield of citral based on reacted dehydrolinalool amounts to 97.2%.

The same catalyst can be employed in over 100 isomerization cycles forthe conversion of dehydrolinalool into citral in similar high yields.

EXAMPLE 8 15.2 g of dehydrolinalool, 0.6g of tris-[dimethylethyl-siloxy]-vanadium oxide and 2.2 g of tricyclohexyl silanolare heated to 140C. for 6.hours in 300 mlof silicon oil. The conversionof dehydrolinalool amounts to The yield of citral based on reacteddehydrolinalool amounts to 90.7%

After distilling off the liquid constituents, the isomerization tocitral can be repeated numerous times after renewed addition ofdehydrolinalool batches.

EXAMPLE 9 EXAMPLE 10 5.2 g of dehydrolinalool, 1.5 g ofbis-[trimethylsiloxy]-[triphenyl-siloxy]-vanadium oxide, 4.5 g oftri(m-tolyl) silanol and 200 ml of high-boiling paraffin oil [D 0.885]are heated to 145C. for 2.5 hours. The conversion of dehydrolinaloolemployed amounts to 92%. The yield of citral based on reacteddehydrolinalool amounts to 93% EXAMPLE 11 15.2 g of dehydrolinalool, 1 gof bis-[triphenylsiloxy]-isopropoxy-vanadium oxide, 1.8 g ofdicyclohexyl methyl silanol and m1 of high-boiling paraffin oil [D 0885]are heated to 140C. for 7.5 hours with the exclusion of moisture. Theconversion of dehydrolinalool employed amounts to 81.7%. The yield ofcitral based on reacted dehydrolinalool amounts to 89%.

EXAMPLE 12 15.2 g of dehydrolinalool, 0.92 g of[triphenylsiloxy]-bis(isopropoxy)-vanadium oxide, 4.3 g of tri( 1-naphthyl) silanol and 170 ml of silicon oil are heated to C. for 6hours. The conversion of dehydrolinalool amounts to 85% The yield ofcitral based on reacted dehydrolinalool amounts to 90% EXAMPLE 13 13.2 gof 3-hydroxy-3-phenyl-prop-1-yne, 2 g of tris-[triphenyl-siloxy]-vanadium oxide, 4.15 g of triphenyl silanol and 100ml of silicon oil are heated to C. for 6 hours with the exclusion ofmoisture. The conversion of the acetylenic carbinol employed amounts to94%. The yield of cinnamaldehyde amounts to 95.1%

EXAMPLE 14 12.6 g of 2-hydroxy-2-methyl-hept-3-yne, 0.7 g oftris-ltrimethyl-siloxy]-vanadium oxide, 2.6 g of tri(npentyl) silanoland ml of high-boiling paraffin oil [D =0.885] are heated at 130C. for 5hours with the exclusion of moisture. The conversion of the acetylenicalcohol employed amounts to 94.5%.- The yield of2-methyl-hept-2-en-4-one amounts to 97.5%.

EXAMPLE 15 10 g of4-ethynyl-4-hydroxy-1,1-ethy1enedioxy-3.5,5-trimethyLcyclohex-Z-en, 0.15 g of hydroquinone, 0.02 ml oftris-[trimethyl-siloxy]-vanadium oxide, 1.75 g of tri(n-propyl) silanoland 100 ml of dry mesitylene are heated to boiling for 16 hours underreflux conditions and with the exclusion of moisture. The solvent andthe excess silanol are distilled off under reduced pressure. Theresidual isomer mixture of cis/trans (4,4-ethylenedioxy-2,6,6-trimethyl-cyclohex-2-en-1- yidene)-acetaldehydeboils at ll125C/0.1 mmHg after rectification in high vacuum. Theconversion of the acetylenic carbinol employed amounts to 88 /1. Thealdehyde is obtained in a yield of 9271.

EXAMPLE l6 Tris-(triphenylsiloxy)vanadium oxide g.), triphenylsilanolg.), stearic acid (0.5 g.), and mineral oil (400 ml.) were heated to150C. under nitrogen and 3,7-dimethyl-7-octen-1-yn-3-ol g.) was added.After 1.5 hours at 150C., the product was distilled under a reducedpressure of less than 1 mmHg. More 3,7-dimethyl-7-octen-l-yn-3-o1 (15g.) was added to the reaction mixture under atmospheric pressure and theproduct was distilled as before after reaction at 150C. for 1.5 hours.The combined distillates of 3,7-dimethyl-2,7-octadienal (29.3 g.)contained no detectable quantity of the isomer 3,7-dimethyl-2,6-octadienal.

EXAMPLE l7 3-Keto-androsta-4,17(20)-dien-20-carboxaldehyde A solution of1.01 g of 17a-ethynyl-androst-4-en- 17B-ol-3-one, 0.103 g. oftris-(triphenyl-siloxy) vanadium oxide 0.029 g of triphenylsilanol, and0.01 g. of benzoic acid in ml of xylene was reflexed for 4 hours. Thesolution was cooled, diluted with hexane and filtered. The filtrate waswashed with 10% sodium bicarbonate, and the wash re-extracted with ethylacetate. The combined organic solutions were dried over anhydrous sodiumsulfate and concentrated to give 1.20 g. of a yellow oil. Chromatographyof the crude product on activity 111 alumina afforded 0.802 g. of acolorless crystalline solid, mp. 1 101 16C.

UV in ethanol, A 242 my. (a 33,300).

1r (KBr), 11 1660, 1595 cm.

Recrystallization from methanol-water gave an analytical sample, m.p.134-136C.

Anal.: calcd for C l-1 0 C80.73, 119.03 found C80.92, H9.02

EXAMPLE 18 3-Methoxy-estra-l ,3 ,5(10),17(20)-tetraene-20-carboxaldehyde 1.04 g. of mestranol (17a-ethynyl-3-methoxy-estra- 1,3,5(10), trien-17B-0l), 0.06 ml. of tris-(trimethylsiloxy)vanadium oxide 414mg. of tri-phenylsilanol, 0.025 g. of benzoic acid, and 20 ml. of xylenewere refluxed for 4 hours. The solution was cooled, diluted with hexane,filtered and concentrated to give 0.924 g. of crude product. Dissolutionof the crude oil in hexane and cooling deposited 0.796 g. of yellowcrystals, m.p. 140150C. Recrystallization from isopropanol gave 0.515 g.of light yellow crystals, m.p. 141155C.

UV in ethanol, A 234 (e 19,900), 242 (e 20,000).

IR (CHCl u 1675 cm.

EXAMPLE 19 Androsta-S ,17(20)-dien-3B-ol-20-carboxaldehyde17a-ethynyl-17B-hyhroxy-androst-5-en-3/3-ol (0.163

g.) was refluxed in xylene (5 ml.) with 50 mg. of tris(triphenylsil0xy)vanadium oxide, 10 mg. of triphenylsilanol, and a few crystals ofbenzoic acid for 3 hours. The solution was poured into 10 ml. of hexaneand filtered. The filtrate was concentrated and the residuechromatographed on activity 111 alumina to afford 85.6 mg. of semi-solidaldehyde.

Nmr 5 9.84 ppm (doublet, aldehyde portons), 1.05 and 0.88 (angularmethyls).

The same amount of catalyst, silanol, benzoic acid and solvent used inExample 19 were utilized in Examples 20-22.

Using the same quantities of catalyst, silanol, benzoic acid andsolvent, the following transformations were effected:

EXAMPLE 20 74.3 mg. of 1,3 ,5(10)-estratriene-17a-ethynyl-3,17B-diol-3-benzoate gave 59.6 mg. of the 1,3,5(10), 17(20)-estratetren-3 -ol-20-carboxaldehyde-3 -benzoate.

Nmr S 9.85 and 10.1 ppm (doublets, two isomeric aldehydes).

EXAMPLE 21 230.9 mg. of racemic norgestrel gave 270.0 mg. of racemic18-homoestra-4,17(20)-dien-3-one-20- carboxaldehyde.

Nmr S g-" 9.75 and 9.93 ppm (doublets, two isomeric aldehydes).

EXAMPLE 22 130.1 mg. of norethynodrel gave 30.5 mg. of estra- 5( 10 17(20)-dien-3-one-20-carboxaldehyde after chromatography.

Nmr 8 9.92 and 10.02 ppm (doublets, two isomeric aldehydes).

' EXAMPLE 23 Vanadium pentoxide (18.2 g.), triphenylsilanol (165.8 g.),1-butanol(50 g.) and xylene were boiled for 24 hours and the waterformed was distilled out. The solution was fitered andtris-(triphenyl-siloxy) vanadium oxide (126,9 g.) crystallized from thefiltrate.

EXAMPLE 24 Tris-(tricyclohexyl-siloxy)vanadium oxide (5.3 g.),tricyclohexysilariol (10.6 g.) stearic acid (0.5 g.) and mineral oil(400 ml.) were heated at 160C. with dehydrolinalool (15 g.) for 2.5hours. Citral was distilled out in 73% yield and the process wasrepeated over times by adding dehydrolinalool to the residue after eachdistillation.

EXAMPLE 25 In an analogous manner to that described in Example 19 andusing the same quantities of catalyst, silanol, benzoic acid and solvent3-keto-19-ethylidene-l7aethynyl-17B-hydroxy-androst-1,4,6-triene gave3-keto- 19-ethylidene-pregna-l ,4,6,17(20)-tetraen-21-al.

NMR 8 0.98 and 1.18 ppm (18-CH3). UV: 6- 26100, 6 9780. IR: 1673, 1660cm" (-CHO); 1609, 1590 cm" (conjugated double bonds).

EXAMPLE 26 A mixture of 20 of 2-hydroxy-2-methyl-3-butynal dimethylacetal, 6 g of triphenyl silanol, ml of parafwherein R is loweralkyl, higher alkyl, cycloalkyl, aryl or aryl lower alkyl, saidcycloalkyl or aryl is unsubsti- 18 tuted or substituted with loweralkyl, R is R or (R Si; m is an integer of from 1 to 3; and n is aninteger of O to 2. with the proviso that the sum of m and n is 3; and atleast 0.05 mole percent, based upon the moles of said siloxy vanadiumoxide of a silanol of the formula:

(R -SiOH wherein R is lower alkyl, higher alkyl, cycloalkyl, aryl oraryl lower alkyl where the cycloalkyl or the aryl is unsubstituted orsubstituted with lower alkyl.

2. The system of claim 1 wherein said silanol is present in an amount offrom 0.05 to 85,000 mole percent, based upon the moles of said siloxyvanadium oxide.

3. The system of claim 1 wherein said vanadate has the formula:

4. The system of claim 3 wherein said vanadate is tri-(triphenyl-siloxy)-vanadium oxide.

I I: i

i i I i UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OFCORRECTION PATENT NO. 3,912,656

DATED October 14, 1975 INVENTO R6) 1 David Arthur Andrews and NathanChadwick Hindley It is certified that error appears in theabove-identified patent and that said Letters Patent are herebycorrected as shown below:

Column 18, line 16, Claim 3 should be Eighteenth Day Of October 1977[SEAL] Attest:

RUTH C. MASON Arresting Oflicer LUTRELLE F. PARKER Acting Commissionerof Patents and Trademarks

1. A CATALYST SYSTEM CONSISTING ESSENTIALLY OF A MIXTURE OF A VANADATECATALYST OF THE FORMULA:
 2. The system of claim 1 wherein said silanolis present in an amount of from 0.05 to 85,000 mole percent, based uponthe moles of said siloxy vanadium oxide.
 3. The system of claim 1wherein said vanadate has the formula: ((R4)3-SiO)3-O
 4. The system ofclaim 3 wherein said vanadate is tri-(triphenyl-siloxy)-vanadium oxide.